Monoclonal antibodies prepared to human myelin-associated glycoprotein were shown to react with a population of human peripheral blood mononuclear cells. The population is similar to the large granular lymphocytes or natural killer cells defined by antibody Leu 7 (also called HNK-1). The population also includes cells exhibiting the Leu 2 marker for suppressor/cytotoxic T cells. The results indicate a shared antigenicity between the nervous system and the immune system and may be relevant to the pathogenesis of demyelinating diseases.Evidence has been accumulating for shared antigenic determinants between the nervous system and the immune system (1-5). This crossreactivity may be involved in the etiopathology of such neurological diseases as multiple sclerosis (5) and myasthenia gravis (3, 4). It recently has been demonstrated that Leu 7 (or HNK-1)-a mouse monoclonal antibody, raised to a human lymphoblastoma, that recognizes human natural killer cells-reacts with components of nervous tissue (6, 7). The myelin-associated glycoprotein (MAG) was identified as a molecule in nervous tissue containing the epitope recognized by this monoclonal antibody (7,8). Furthermore, the epitope in MAG is in its carbohydrate moieties (9) and also is in other glycoconjugates of peripheral nerve (9, 10).In this paper, we describe the reaction of mouse monoclonal antibodies prepared to MAG (11) with a subpopulation of human peripheral blood mononuclear cells. Further experiments show that this population is similar to the large granular lymphocytes (LGL) recognized by Leu 7. The results indicate that MAG and a population of peripheral blood lymphocytes share a common antigenic determinant. This finding may have relevance in the pathogenesis of demyelinating diseases.MATERIALS AND METHODS Monoclonal Antibodies. Murine monoclonal antibodies to MAG were produced as described (11). Briefly, P3X63-Ag8.653 myeloma cells were fused with spleen cells from a female NZB/N mouse immunized with purified human MAG isolated from the central nervous system. Hybrids and subsequent clones were screened for antibody production to MAG by using a solid-phase enzyme immunoassay system. The following monoclonal antibodies were used in this study: G7C8, E8B8, and C6D9 of the IgM subclass with K light chains, which react with determinants in the carbohydrate moieties of human MAG; F7F7, an IgG2b subclass antibody with K light chains, which also reacts with a carbohydrate determinant of human MAG; and B11F7 (IgG2b) and D7E10 (IgGl) with K light chains, which react with polypeptide determinants of human and rat MAG. The hybridomas were grown as ascites tumors in pristane-primed NIH/Swiss nude mice. Monoclonal antibodies were purified from ascites fluid by Sepharose-protein A affinity chromatography (12) for antibodies F7F7 and B11F7 and by euglobulin fractionation followed by Sephadex G-200 chromatography (13) for antibody G7C8. Hybridoma HNK-1 (14) was purchased from the American Type Culture Collection. The hybridoma was grown and the monoclonal a...